chr15-82849770-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004839.4(HOMER2):c.977T>C(p.Ile326Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000093 ( 0 hom. )
Consequence
HOMER2
NM_004839.4 missense
NM_004839.4 missense
Scores
8
8
1
Clinical Significance
Conservation
PhyloP100: 8.43
Genes affected
HOMER2 (HGNC:17513): (homer scaffold protein 2) This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. The encoded protein is a postsynaptic density scaffolding protein. Alternative splicing results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 14. [provided by RefSeq, Jun 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.819
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HOMER2 | NM_004839.4 | c.977T>C | p.Ile326Thr | missense_variant | 9/9 | ENST00000450735.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HOMER2 | ENST00000450735.7 | c.977T>C | p.Ile326Thr | missense_variant | 9/9 | 1 | NM_004839.4 | ||
HOMER2 | ENST00000304231.12 | c.1010T>C | p.Ile337Thr | missense_variant | 9/9 | 5 | P1 | ||
HOMER2 | ENST00000558552.1 | n.857T>C | non_coding_transcript_exon_variant | 3/3 | 2 | ||||
HOMER2 | ENST00000558090.2 | upstream_gene_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152098Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000602 AC: 15AN: 249166Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135192
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GnomAD4 exome AF: 0.0000930 AC: 136AN: 1461692Hom.: 0 Cov.: 31 AF XY: 0.0000921 AC XY: 67AN XY: 727130
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152098Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7AN XY: 74280
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2023 | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 326 of the HOMER2 protein (p.Ile326Thr). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1475075). This variant has not been reported in the literature in individuals affected with HOMER2-related conditions. This variant is present in population databases (rs779466414, gnomAD 0.01%). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
0.79
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at